PRINCETON, N.J.--(EON: Enhanced Online News)--Bristol-Myers
Squibb Company (NYSE: BMY) announced today that the U.S. Food and
Drug Administration (FDA) has accepted its supplemental Biologics
License Application (sBLA) for priority review of Opdivo
(nivolumab) plus Yervoy (ipilimumab) to treat intermediate- and
poor-risk patients with advanced renal cell carcinoma (RCC). The FDA
also previously granted Breakthrough Therapy Designation for this
application, which is the 2nd indication for which the Opdivo
plus Yervoy combination has received this designation.

“Breakthrough therapy designation and today’s
filing acceptance for the Opdivo plus Yervoy combination
are an important step in our ongoing efforts to advance therapies to
address a high unmet need in first-line treatment of kidney cancer in
intermediate- and poor-risk patients.”

“At BMS, we hope to provide treatment options to patients with advanced
forms of renal cell carcinoma,” said Murdo
Gordon, executive vice president and chief commercial officer,
Bristol-Myers Squibb. “Breakthrough therapy designation and today’s
filing acceptance for the Opdivo plus Yervoy combination
are an important step in our ongoing efforts to advance therapies to
address a high unmet need in first-line treatment of kidney cancer in
intermediate- and poor-risk patients.”

The application is based on data from the phase 3 CheckMate -214 study,
which was stopped early based on the recommendation of an independent
Data Monitoring Committee following a planned interim analysis of
overall survival. The results of the study were recently presented at
the European Society for Medical Oncology (ESMO) 2017 Congress.

The Breakthrough Therapy Designation is an FDA program intended to
expedite the development and review of medicines with signals of
potential clinical benefit in serious diseases to help ensure patients
have access to new therapies as soon as possible.

The application has an action date of April 16, 2018.

About CheckMate -214CheckMate
-214 is a phase 3, randomized, open-label study evaluating the
combination of Opdivo plus Yervoy versus sunitinib in
patients with previously untreated advanced or metastatic renal cell
carcinoma. Patients in the combination group received Opdivo 3
mg/kg plus Yervoy 1 mg/kg every 3 weeks for 4 doses followed by Opdivo
3 mg/kg every 2 weeks. Patients in the comparator group received
sunitinib 50 mg once daily for 4 weeks, followed by 2 weeks off before
continuation of treatment. Patients were treated until progression or
unacceptable toxic effects. The primary endpoints of the trial are
overall survival, progression-free survival and objective response rate
in an intermediate to poor-risk patient population (approximately 75% of
patients). Safety is a secondary endpoint. The study met the co-primary
endpoints of improved overall survival and objective response rate
compared to sunitinib in intermediate- and poor-risk patients. While the
combination demonstrated an improvement in progression-free survival
relative to sunitinib, another co-primary endpoint, it did not reach
statistical significance.

Adverse events (AEs) leading to discontinuation were reported in 22% of
patients (547) in the combination group, compared with 12% of patients
in the sunitinib group (535). The most common grade 3/4 AEs in the
combination group were fatigue (4%), diarrhea (4%), rash (2%), nausea
(2%), and, in less than 1% each, pruritus, hypothyroidism, vomiting and
hypertension. In the sunitinib group, the most common grade 3/4 AEs were
hypertension (16%), fatigue (9%), Palmar-plantar erythrodysaesthesia
syndrome (9%), stomatitis (3%), mucosal inflammation (3%), vomiting
(2%), nausea (1%), decreased appetite (1%), hypothyroidism (<1%) and
dysgeusia (<1%). There were seven treatment-related deaths in the
combination group and four in the sunitinib group.

About Renal Cell CarcinomaRenal
cell carcinoma (RCC) is the most common type of kidney cancer in adults,
accounting for more than 100,000 deaths worldwide each year. Clear-cell
RCC is the most prevalent type of RCC and constitutes 80% to 90% of all
patients. RCC is approximately twice as common in men as in women, with
the highest rates of the disease in North America and Europe. Globally,
the five-year survival rate for those diagnosed with metastatic, or
advanced, kidney cancer is 12.1%.

Bristol-Myers Squibb & Immuno-Oncology:
Advancing Oncology ResearchAt Bristol-Myers Squibb,
patients are at the center of everything we do. Our vision for the
future of cancer care is focused on researching and developing
transformational Immuno-Oncology (I-O) medicines for hard-to-treat
cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive
portfolio of investigational compounds and approved agents. Our
differentiated clinical development program is studying broad patient
populations across more than 50 types of cancers with 14 clinical-stage
molecules designed to target different immune system pathways. Our deep
expertise and innovative clinical trial designs position us to advance
I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O radiation
therapies across multiple tumors and potentially deliver the next wave
of therapies with a sense of urgency. We also continue to pioneer
research that will help facilitate a deeper understanding of the role of
immune biomarkers and how patients’ tumor biology can be used as a guide
for treatment decisions throughout their journey.

We understand making the promise of I-O a reality for the many patients
who may benefit from these therapies requires not only innovation on our
part but also close collaboration with leading experts in the field. Our
partnerships with academia, government, advocacy and biotech companies
support our collective goal of providing new treatment options to
advance the standards of clinical practice.

About OpdivoOpdivo
is a programmed death-1 (PD-1) immune checkpoint inhibitor that is
designed to uniquely harness the body’s own immune system to help
restore anti-tumor immune response. By harnessing the body’s own immune
system to fight cancer, Opdivo has become an important treatment
option across multiple cancers.

Opdivo’s leading global development program is based on
Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials across all
phases, including Phase 3, in a variety of tumor types. To date, the Opdivo
clinical development program has enrolled more than 25,000 patients. The Opdivo
trials have contributed to gaining a deeper understanding of the
potential role of biomarkers in patient care, particularly regarding how
patients may benefit from Opdivo across the continuum of PD-L1
expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world. Opdivo
is currently approved in more than 60 countries, including the United
States, the European Union and Japan. In October 2015, the company’s Opdivo
and Yervoy combination regimen was the first Immuno-Oncology
combination to receive regulatory approval for the treatment of
metastatic melanoma and is currently approved in more than 50 countries,
including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®

OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY®
(ipilimumab), is indicated for the treatment of patients with
unresectable or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy. Patients with EGFR
or ALK genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. This indication is approved under
accelerated approval based on overall response rate. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with recurrent or metastatic squamous cell carcinoma of the
head and neck (SCCHN) with disease progression on or after
platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with locally advanced or metastatic urothelial carcinoma who
have disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of neoadjuvant
or adjuvant treatment with platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of adult
and pediatric (12 years and older) patients with microsatellite
instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic
colorectal cancer (CRC) that has progressed following treatment with a
fluoropyrimidine, oxaliplatin, and irinotecan. This indication is
approved under accelerated approval based on overall response rate and
duration of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib. This indication is approved under accelerated
approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.

U.S. FDA-APPROVED INDICATIONS FOR YERVOY®

YERVOY® (ipilimumab) is indicated for the treatment of unresectable or
metastatic melanoma in adults and pediatric patients (12 years and
older).

YERVOY® (ipilimumab) is indicated for the adjuvant treatment of patients
with cutaneous melanoma with pathologic involvement of regional lymph
nodes of more than 1 mm who have undergone complete resection, including
total lymphadenectomy.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ system;
however, the most common severe immune-mediated adverse reactions are
enterocolitis, hepatitis, dermatitis (including toxic epidermal
necrolysis), neuropathy, and endocrinopathy. The majority of these
immune-mediated reactions initially manifested during treatment;
however, a minority occurred weeks to months after discontinuation of
YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis,
neuropathy, and endocrinopathy and evaluate clinical chemistries
including liver function tests (LFTs), adrenocorticotropic hormone
(ACTH) level, and thyroid function tests at baseline and before each
dose.

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and
symptoms of colitis. Administer corticosteroids for Grade 2 (of more
than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for
Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent
colitis upon re-initiation of OPDIVO. When administered with YERVOY,
withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for
Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO
monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of
patients. In patients receiving OPDIVO with YERVOY, immune-mediated
colitis occurred in 26% (107/407) of patients including three fatal
cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening,
or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal
signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%)
patients. Across all YERVOY-treated patients in that study (n=511), 5
(1%) developed intestinal perforation, 4 (0.8%) died as a result of
complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. For patients without HCC, withhold OPDIVO for Grade 2 and
permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC,
withhold OPDIVO and administer corticosteroids if AST/ALT is within
normal limits at baseline and increases to >3 and up to 5 times the
upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at
baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT
is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10
times the ULN. Permanently discontinue OPDIVO and administer
corticosteroids if AST or ALT increases to >10 times the ULN or total
bilirubin increases >3 times the ULN. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of
patients. In patients receiving OPDIVO with YERVOY, immune-mediated
hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients.
All 9 patients had hypopituitarism, and some had additional concomitant
endocrinopathies such as adrenal insufficiency, hypogonadism, and
hypothyroidism. 6 of the 9 patients were hospitalized for severe
endocrinopathies.

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients
with neurologic symptoms may include, but not be limited to,
consultation with a neurologist, brain MRI, and lumbar puncture.
Withhold OPDIVO in patients with new-onset moderate to severe neurologic
signs or symptoms and evaluate to rule out other causes. If other
etiologies are ruled out, administer corticosteroids and permanently
discontinue OPDIVO for immune-mediated encephalitis. In patients
receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of
patients. Fatal limbic encephalitis occurred in one patient after 7.2
months of exposure despite discontinuation of OPDIVO and administration
of corticosteroids. Encephalitis occurred in one patient receiving
OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

OPDIVO can cause severe infusion reactions, which have been reported in
<1.0% of patients in clinical trials. Discontinue OPDIVO in patients
with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of
infusion in patients with Grade 1 or 2. In patients receiving OPDIVO
monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of
patients. In patients receiving OPDIVO with YERVOY, infusion-related
reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received
allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients
from Checkmate 205 and 039, who underwent allogeneic HSCT after
discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with
myeloablative conditioning). Thirty-five percent (6/17) of patients died
from complications of allogeneic HSCT after OPDIVO. Five deaths occurred
in the setting of severe or refractory GVHD. Grade 3 or higher acute
GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was
reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome,
without an identified infectious cause, was reported in 35% (n=6) of
patients. Two cases of encephalitis were reported: Grade 3 (n=1)
lymphocytic encephalitis without an identified infectious cause, and
Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive
disease (VOD) occurred in one patient, who received reduced-intensity
conditioned allogeneic HSCT and died of GVHD and multi-organ failure.
Other cases of hepatic VOD after reduced-intensity conditioned
allogeneic HSCT have also been reported in patients with lymphoma who
received a PD-1 receptor blocking antibody before transplantation. Cases
of fatal hyperacute GVHD have also been reported. These complications
may occur despite intervening therapy between PD-1 blockade and
allogeneic HSCT.

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal
harm when administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential to
use effective contraception during treatment with an OPDIVO- or YERVOY-
containing regimen and for at least 5 months after the last dose of
OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk.
Because many drugs, including antibodies, are excreted in human milk and
because of the potential for serious adverse reactions in nursing
infants from an OPDIVO-containing regimen, advise women to discontinue
breastfeeding during treatment. Advise women to discontinue nursing
during treatment with YERVOY and for 3 months following the final dose.

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse
reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue
(41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please see U.S. Full Prescribing Information for OPDIVO
and YERVOY,
including Boxed WARNING regarding immune-mediated adverse reactions
for YERVOY.

About the Bristol-Myers Squibb and Ono
Pharmaceutical Co., Ltd. Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co.,
Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to
develop and commercialize Opdivo globally except in Japan, South Korea
and Taiwan, where Ono had retained all rights to the compound at the
time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded
the companies’ strategic collaboration agreement to jointly develop and
commercialize multiple immunotherapies – as single agents and
combination regimens – for patients with cancer in Japan, South Korea
and Taiwan.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information about
Bristol-Myers Squibb, visit us at BMS.com
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Bristol-Myers Squibb Forward-Looking Statement

This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that Opdivo and Yervoy will
receive regulatory approval for an additional indication.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers Squibb's
business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the
year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and
our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no
obligation to publicly update any forward-looking statement, whether as
a result of new information, future events or otherwise.